Congestive heart failure (CHF; also called chronic heart failure) is a clinical syndrome associated with vascular abnormalities characterized by an elevated baseline vascular tone and impaired response to NO-mediated vasodilatation (Francis and Cohn (1990) FASEB J. 4:3068; and Negrao et al. (2000) Am. J. Physiol. 278:H168-H174). The mechanism leading to these changes in the vasculature is unknown.
The standard regimen for patients with the clinical syndrome of heart failure consists of a vasodilator (most commonly an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker (ARB) or hydralazine), a β-blocker, a nitrate and, if necessary for volume control, a diuretic. ACE is involved in formation of angiotensin II, which causes constriction of arteries in the body and thereby elevates blood pressure. ACE inhibitors such as captopril (1-[(2S)-3-mercapto-2-methylpropionyl]-L-proline) lower blood pressure by inhibiting the formation of angiotensin II, thus relaxing the arteries. Relaxing the arteries not only lowers blood pressure, but also improves the pumping efficiency of a failing heart and improves cardiac output in patients with heart failure.
Currently, the medication dose required for an individual patient to achieve a clinical response is guided only by clinical expertise. There is no test that can be used to indicate individual patient prognosis and/or response (either beneficial or adverse) to therapy.